Type I or Insulin-Dependent Diabetes Mellitus (IDDM) arises in genetically predisposed individuals as a consequence of immune-mediated destruction of the pancreatic islet insulin secreting cells. The onset of clinical symptoms of diabetes represents the end point of a chronic progressive decline in beta-cell function, and it appears only when the majority of beta-cells have been lost. Since IDDM develops insidiously, often years after the induction of the pathogenic immune-mediated destructive process, it can be predicted using immunological markers and tests of insulin secretion. The "Diabetes Prevention Trial of Type I Diabetes" (DPT-1) has been designed to test whether intervention during the prodromal period of the disease can delay its clinical onset. It is possible to identify impending clinical IDDM through the detection of autoantibodies against self-antigens of the pancreatic beta-cells. Since first degree relatives of probands with IDDM have more than ten-fold the risk of IDDM in the general population, the DPT-1 will focus on such relatives. Their initial blood (serum) screening will be for islet cell autoantibodies (ICA) detectable by the indirect immunofluorescence of cytoplasmic islet cell antigens in sections of normal human pancreas. Those individuals found to have ICA will then be staged into one of four different categories of risk of IDDM, dependent upon their point of progression to the clinical disease. IDDM risk assessment in non-diabetic relatives is based on a number of factors, including: genetic susceptibility, age, the presence of ICA especially if found together with insulin autoantibodies (IAA), and the degree of loss of first phase (1+3 minute) plasma insulin response (FPIR) during an intravenous glucose tolerance test (IVGTT). In the DPT-1, "High Risk" relatives will be those that have been predicted to have at least a 50 percent probability of developing IDDM within the next five years on the basis of positive ICA and low FPIR to IVGTT. Moderate risk relatives are those with positive ICA, but normal FPIR to IVGTT. This group is further divisible into those with an "Intermediate Risk' on account of positive IAA and those with only a 'Modest Risk' who are IAA negative. The 'Low Risk' relatives lack ICA.